Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia

Minori Koga, Hiroki Ishiguro, Saori Yazaki, Yasue Horiuchi, Makoto Arai, Kazuhiro Niizato, Shuji Iritani, Masanari Itokawa, Toshiya Inada, Nakao Iwata, Norio Ozaki, Hiroshi Ujike, Hiroshi Kunugi, Tsukasa Sasaki, Makoto Takahashi, Yuichiro Watanabe, Toshiyuki Someya, Akiyoshi Kakita, Hitoshi Takahashi, Hiroyuki Nawa & 3 others Christian Muchardt, Moshe Yaniv, Tadao Arinami

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 × 10 -5 ) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 × 10 -6 ) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.

Original languageEnglish
Pages (from-to)2483-2494
Number of pages12
JournalHuman molecular genetics
Volume18
Issue number13
DOIs
Publication statusPublished - 22-06-2009

Fingerprint

Chromatin Assembly and Disassembly
Schizophrenia
Prefrontal Cortex
Knockout Mice
Genes
Single Nucleotide Polymorphism
Alleles
Neurobiology
Linkage Disequilibrium
Interpersonal Relations
Genomics
Small Interfering RNA
Antipsychotic Agents
Biomedical Research
Databases
Gene Expression
Brain
Pharmaceutical Preparations
Population
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Koga, M., Ishiguro, H., Yazaki, S., Horiuchi, Y., Arai, M., Niizato, K., ... Arinami, T. (2009). Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. Human molecular genetics, 18(13), 2483-2494. https://doi.org/10.1093/hmg/ddp166
Koga, Minori ; Ishiguro, Hiroki ; Yazaki, Saori ; Horiuchi, Yasue ; Arai, Makoto ; Niizato, Kazuhiro ; Iritani, Shuji ; Itokawa, Masanari ; Inada, Toshiya ; Iwata, Nakao ; Ozaki, Norio ; Ujike, Hiroshi ; Kunugi, Hiroshi ; Sasaki, Tsukasa ; Takahashi, Makoto ; Watanabe, Yuichiro ; Someya, Toshiyuki ; Kakita, Akiyoshi ; Takahashi, Hitoshi ; Nawa, Hiroyuki ; Muchardt, Christian ; Yaniv, Moshe ; Arinami, Tadao. / Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. In: Human molecular genetics. 2009 ; Vol. 18, No. 13. pp. 2483-2494.
@article{e6ce22e710754ca787ef36a7cdc574fa,
title = "Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia",
abstract = "Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 × 10 -5 ) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 × 10 -6 ) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.",
author = "Minori Koga and Hiroki Ishiguro and Saori Yazaki and Yasue Horiuchi and Makoto Arai and Kazuhiro Niizato and Shuji Iritani and Masanari Itokawa and Toshiya Inada and Nakao Iwata and Norio Ozaki and Hiroshi Ujike and Hiroshi Kunugi and Tsukasa Sasaki and Makoto Takahashi and Yuichiro Watanabe and Toshiyuki Someya and Akiyoshi Kakita and Hitoshi Takahashi and Hiroyuki Nawa and Christian Muchardt and Moshe Yaniv and Tadao Arinami",
year = "2009",
month = "6",
day = "22",
doi = "10.1093/hmg/ddp166",
language = "English",
volume = "18",
pages = "2483--2494",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "13",

}

Koga, M, Ishiguro, H, Yazaki, S, Horiuchi, Y, Arai, M, Niizato, K, Iritani, S, Itokawa, M, Inada, T, Iwata, N, Ozaki, N, Ujike, H, Kunugi, H, Sasaki, T, Takahashi, M, Watanabe, Y, Someya, T, Kakita, A, Takahashi, H, Nawa, H, Muchardt, C, Yaniv, M & Arinami, T 2009, 'Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia', Human molecular genetics, vol. 18, no. 13, pp. 2483-2494. https://doi.org/10.1093/hmg/ddp166

Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. / Koga, Minori; Ishiguro, Hiroki; Yazaki, Saori; Horiuchi, Yasue; Arai, Makoto; Niizato, Kazuhiro; Iritani, Shuji; Itokawa, Masanari; Inada, Toshiya; Iwata, Nakao; Ozaki, Norio; Ujike, Hiroshi; Kunugi, Hiroshi; Sasaki, Tsukasa; Takahashi, Makoto; Watanabe, Yuichiro; Someya, Toshiyuki; Kakita, Akiyoshi; Takahashi, Hitoshi; Nawa, Hiroyuki; Muchardt, Christian; Yaniv, Moshe; Arinami, Tadao.

In: Human molecular genetics, Vol. 18, No. 13, 22.06.2009, p. 2483-2494.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia

AU - Koga, Minori

AU - Ishiguro, Hiroki

AU - Yazaki, Saori

AU - Horiuchi, Yasue

AU - Arai, Makoto

AU - Niizato, Kazuhiro

AU - Iritani, Shuji

AU - Itokawa, Masanari

AU - Inada, Toshiya

AU - Iwata, Nakao

AU - Ozaki, Norio

AU - Ujike, Hiroshi

AU - Kunugi, Hiroshi

AU - Sasaki, Tsukasa

AU - Takahashi, Makoto

AU - Watanabe, Yuichiro

AU - Someya, Toshiyuki

AU - Kakita, Akiyoshi

AU - Takahashi, Hitoshi

AU - Nawa, Hiroyuki

AU - Muchardt, Christian

AU - Yaniv, Moshe

AU - Arinami, Tadao

PY - 2009/6/22

Y1 - 2009/6/22

N2 - Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 × 10 -5 ) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 × 10 -6 ) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.

AB - Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 × 10 -5 ) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 × 10 -6 ) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.

UR - http://www.scopus.com/inward/record.url?scp=67249131065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67249131065&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddp166

DO - 10.1093/hmg/ddp166

M3 - Article

VL - 18

SP - 2483

EP - 2494

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 13

ER -

Koga M, Ishiguro H, Yazaki S, Horiuchi Y, Arai M, Niizato K et al. Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. Human molecular genetics. 2009 Jun 22;18(13):2483-2494. https://doi.org/10.1093/hmg/ddp166